Two-Year Efficacy and Safety of Ravulizumab in Adults and Children with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of Two Phase 3 Studies

Background Ravulizumab, a humanized anti-complement C5 monoclonal antibody designed by targeted modification of eculizumab to achieve an extended half-life, is approved to treat aHUS in the USA (2019), EU and Japan (2020). Data at 26 weeks (wk) and 1 year (yr) from the phase 3 studies of ravulizumab in adults and children with aHUS have been published. Here we report 2-yr data from these trials. Methods Efficacy and safety data from ravulizumab clinical trials in adults naïve to complement inhibitor treatment (NCT02949128), and in children either naïve to (naïve) or switched from (switch) eculizumab (NCT03131219), were assessed at 2 yr and presented alongside data from the initial 26-wk evaluation periods; patients were dosed every 8 wk (adult), or every 4 or 8 wk (children), according to body weight. Descriptive statistical analyses were conducted on these data. No statistical comparisons between data at 26 wk and 2 yr, or between trials, were conducted. Results Efficacy data in adults and treatment-naïve children are presented in the Table. Complete thrombotic microangiopathy (TMA) response (platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, met concurrently at 2 separate assessments, at least 4 wk apart) was achieved in more patients at 2 yr vs 26 wk in both studies (adult: 34 [61%) vs 30 [54%]; naïve: 18 [90%] vs 15 [75%]). All complete TMA response components were either numerically improved or maintained at 2 yr vs 26 wk. Kidney function continued to improve, with the median change in estimated glomerular filtration rate from baseline numerically increasing at 2 yr vs 26 wk in both adults (35 vs 29 mL/min/1.73m 2) and naïve children (82.5 vs 80 mL/min/1.73m 2). Most patients receiving dialysis at baseline were able to discontinue dialysis at 26 wk; this was sustained in adults (67% vs 67%) while all naïve children receiving dialysis at baseline had discontinued by 2 yr (83% vs 100%). No patients who discontinued dialysis by 26 wk subsequently restarted. Chronic kidney disease (CKD) stage improved in most patients through 26 wk in both studies (adult, 68%; naïve, 88%); improvements were sustained at 2 yr (adult, 71%; naïve, 94%). No naïve children experienced a worsening of CKD stage at 2 yr. Improvements from baseline in quality of life were seen at both 26 wk and 2 yr, as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (adults: 20 vs 12; naïve: 10 vs 8), EQ-